The close interaction and relationships among the different projects make this a program project. The three major projects are: 1. Therapy of Fungus Infection. We continue to study the effects and mechanisms of action of amphotericin B on fungi and host cells, animal models of infection, and finally in clinical studies. Our hope is to learn how this drug works on fungi and also on the host so that its therapeutic potential can be maximally exploited. In addition, these kinds of studies represent a model system of how other similar therapeutic agents should be studied. 2. Pathogenesis of Histoplasmosis. We study virulence factors in H. capsulatum and host resistance to infection with this fungus to learn something of host-parasite interactions in this disease. A subproject deals with antibody responses to common epitopes in different fungi. These studies are also relevant to host-parasite interactions and may also provide strategies for devising new diagnostic reagents and vaccines. 3. The molecular Biology of Phase Transition of Histoplasma capsulatum. We will complete our studies on the biochemistry and physiology of phase transition in H. capsulatum. We will also begin studies on cloning the genes involved in the phase transition and characterizing these genes.